The sphingolipid metabolic pathway is initiated by the incorporation of palmitoyl CoA, derivative of fatty acids, and ultimately provides substrates for the synthesis of other lipids. Thus the sphingolipid metabolic pathway is highly integrated with other dietary and structural lipid metabolic pathways. Furthermore, the sphingolipid metabolites themselves are bioactive and alter cell metabolism via signaling pathways. We have developed, and continue to develop genetically altered mice with modified expression of key sphingolipid enzyme activities in order to study the role of the pathway in metabolism including their role in diabetes and obesity.